WEBVTT 00:00:01.229 --> 00:00:04.570 For today's episode, Dr. Richard Frey returns 00:00:04.570 --> 00:00:08.169 to share some updates with his research and clinical 00:00:08.169 --> 00:00:13.949 work. Dr. Frey is an MD, board certified in pediatrics, 00:00:14.349 --> 00:00:18.370 neurology with special competence in child neurology, 00:00:18.370 --> 00:00:22.050 and is a certified principal investigator. In 00:00:22.050 --> 00:00:26.190 addition, Dr. Frey is a PhD in physiology and 00:00:26.190 --> 00:00:29.850 biophysics. This episode is all about Luke O 00:00:29.850 --> 00:00:34.539 'Boren. Dr. Fry shares many great routes to learning 00:00:34.539 --> 00:00:37.659 more about leukoborne, including his upcoming 00:00:37.659 --> 00:00:43.799 book, Folate Fix, and two websites, Neurological 00:00:43.799 --> 00:00:48.759 Health Foundation and Healthy Child Guide. Please 00:00:48.759 --> 00:00:51.840 see the show notes for links to all of these 00:00:51.840 --> 00:00:56.380 wonderful resources. But first, a message about 00:00:56.380 --> 00:01:00.119 daylight computer and chroma. I would like to 00:01:00.119 --> 00:01:03.659 take a moment and mention a pressing issue we 00:01:03.659 --> 00:01:09.640 are seeing in our modern world and that is tech 00:01:09.640 --> 00:01:15.359 use and tech light. The data are impressive and 00:01:15.359 --> 00:01:19.799 concerning on isolated wavelengths of light, 00:01:20.439 --> 00:01:24.879 especially shorter wavelengths, which is blue 00:01:24.879 --> 00:01:30.719 light. For those that don't know, We have chromophores, 00:01:31.159 --> 00:01:34.900 which are special proteins that absorbs specific 00:01:34.900 --> 00:01:39.819 wavelengths of light. For blue light, the light 00:01:39.819 --> 00:01:44.200 that is LED light and tech light, that protein 00:01:44.200 --> 00:01:50.019 is called melanopsin. Melanopsin is responsible 00:01:50.019 --> 00:01:55.260 for our circadian biology, physiology, and cell 00:01:55.260 --> 00:02:00.390 functioning. hormone regulation, and even a connection 00:02:00.390 --> 00:02:06.769 to an area huge for mood. A consideration we 00:02:06.769 --> 00:02:11.250 should include is this protein was not even discovered 00:02:11.250 --> 00:02:17.870 until 1998. It seems important for us to understand 00:02:17.870 --> 00:02:22.469 how our biology uses the different wavelengths 00:02:22.469 --> 00:02:27.169 of light. for various aspects of our biology. 00:02:28.770 --> 00:02:32.590 This blue light chromophore is our master controller, 00:02:33.610 --> 00:02:38.330 our master clock. Remember circadian rhythm is 00:02:38.330 --> 00:02:44.430 a two -part process, two independent parts, light 00:02:44.430 --> 00:02:51.069 and dark. For a quick reference, see the 2017 00:02:51.069 --> 00:02:56.419 Nobel Prize in Physiology and medicine. But for 00:02:56.419 --> 00:02:59.719 now, I have something exciting. I want to introduce 00:02:59.719 --> 00:03:02.620 a product unlike any other product available. 00:03:03.539 --> 00:03:08.099 A highlight is the product from Daylight Computer 00:03:08.099 --> 00:03:11.580 Company created their product based on these 00:03:11.580 --> 00:03:16.539 factors. The Daylight Computer is completely 00:03:16.539 --> 00:03:22.039 blue light free. It has no flicker, short wavelength 00:03:22.039 --> 00:03:26.680 flicker. is extremely harmful for our eyes and 00:03:26.680 --> 00:03:30.479 downstream biology. Light flicker is constantly 00:03:30.479 --> 00:03:34.159 turning our central nervous system on and off. 00:03:35.000 --> 00:03:38.479 Essentially it is like going to a light switch 00:03:38.479 --> 00:03:42.879 and repeatedly turning it on and off. The problem 00:03:42.879 --> 00:03:48.900 is blue light and LED light does this and it 00:03:48.900 --> 00:03:52.150 is so rapid You cannot even perceive this in 00:03:52.150 --> 00:03:57.650 real time. The daylight computer is the lowest 00:03:57.650 --> 00:04:01.569 stimulation and foremost for sensory sensitive 00:04:01.569 --> 00:04:06.870 users. It is no question that the alternative 00:04:06.870 --> 00:04:12.169 product, especially when used at night, do not 00:04:12.169 --> 00:04:16.589 address or consider this in their product. It 00:04:16.589 --> 00:04:21.610 is so toxic to human biology. Big tech corporations 00:04:21.610 --> 00:04:26.250 have patents on how their short wavelength implicate 00:04:26.250 --> 00:04:31.850 the human nervous system. And a bonus, despite 00:04:31.850 --> 00:04:36.009 daylight computer not having backlight, it is 00:04:36.009 --> 00:04:40.389 very functional for outdoor use. And of course, 00:04:41.209 --> 00:04:46.170 increased sunlight is always preferred. I am 00:04:46.170 --> 00:04:49.550 happy to offer a discount for the Daylight Computer. 00:04:50.610 --> 00:04:55.709 You can use the code Autism for a $25 off coupon. 00:04:57.209 --> 00:05:01.569 Again, use the code Autism and the discount code 00:05:01.569 --> 00:05:06.730 for $25 off. See the link in the show notes to 00:05:06.730 --> 00:05:09.930 Daylight Computer Company or just give it a quick 00:05:09.930 --> 00:05:14.029 search in your internet browser. Use the code 00:05:14.029 --> 00:05:20.230 Autism. for $25 off. I would like to mention 00:05:20.230 --> 00:05:26.529 Chroma, lights designed for humans. Chroma, a 00:05:26.529 --> 00:05:30.930 Seattle -based innovator founded by ex -NASA 00:05:30.930 --> 00:05:35.370 and Air Force engineer Michael Shapiro, is on 00:05:35.370 --> 00:05:38.889 a mission to enhance physical and mental health 00:05:38.889 --> 00:05:44.029 with purpose -built devices, unlocking peak human 00:05:44.029 --> 00:05:49.699 health. cognitive function and performance. Shapiro 00:05:49.699 --> 00:05:52.560 launched Chroma to restore the natural light 00:05:52.560 --> 00:05:57.319 lost to screens in indoor living and delivers 00:05:57.319 --> 00:06:01.160 faster recovery, sharper minds and better sleep. 00:06:02.240 --> 00:06:06.160 Their products hit hard. The Iron Forge speeds 00:06:06.160 --> 00:06:10.160 muscle repair with red and near -infrared light, 00:06:10.819 --> 00:06:14.060 while the Skylight mimics sunlight. to boost 00:06:14.060 --> 00:06:19.759 sleep and energy. A standout, the Forge Lamp, 00:06:20.120 --> 00:06:25.120 is a portable gem that fires 660 nanometer and 00:06:25.120 --> 00:06:30.860 850 nanometer light to energize mitochondria 00:06:30.860 --> 00:06:35.500 and heal tissues on the go. Remember the four 00:06:35.500 --> 00:06:38.600 red light chromophores on cytochrome c -oxidase 00:06:38.600 --> 00:06:42.480 frequently talked about in the podcast. This 00:06:42.480 --> 00:06:46.720 is why. Their products are built with military 00:06:46.720 --> 00:06:52.660 -grade durability that have lasting impact. Chromis 00:06:52.660 --> 00:06:58.560 Tech fuses precision and power. Gallium titride 00:06:58.560 --> 00:07:02.699 power supplies. Smaller, cooler, and stronger 00:07:02.699 --> 00:07:06.899 than silicon. Provide flicker -free light that's 00:07:06.899 --> 00:07:11.629 easy on the eyes. High -powered LEDs target key 00:07:11.629 --> 00:07:16.290 wavelengths for skin, tissue, and cellular health 00:07:16.290 --> 00:07:20.050 with smart heat management for the lasting impact. 00:07:21.050 --> 00:07:24.449 Every design decision Chroma makes serves a purpose 00:07:24.449 --> 00:07:29.009 to create devices that are precise, durable, 00:07:29.449 --> 00:07:34.750 and effective for improving human life. Remember, 00:07:35.209 --> 00:07:37.769 humans use different wavelengths of light for 00:07:37.769 --> 00:07:42.759 different functions of life. Remember when I 00:07:42.759 --> 00:07:49.819 ask, what do you think light is? Chroma designs 00:07:49.819 --> 00:07:54.720 with our biology in mind. From sleep aids and 00:07:54.720 --> 00:07:59.399 wound healing to mitochondrial energy, full body 00:07:59.399 --> 00:08:02.860 lights and blue light blocking glasses. They 00:08:02.860 --> 00:08:07.920 are US made and Chroma ships globally and accepts 00:08:07.920 --> 00:08:15.750 FSA and HSA. payments. Use autism at checkout 00:08:15.750 --> 00:08:22.430 for a 10 % off discount. That's autism at checkout 00:08:22.430 --> 00:08:30.110 for a 10 % off discount. Dr. Frey, thank you 00:08:30.110 --> 00:08:32.889 for joining again. I'm super excited about this 00:08:32.889 --> 00:08:37.259 and the recent news with Lickle Warren. Yeah, 00:08:37.259 --> 00:08:40.240 thank you so much for inviting me. I'm glad that 00:08:40.240 --> 00:08:42.779 there's some interest in this. We've had a lot 00:08:42.779 --> 00:08:45.820 of success, and I hope that other people can 00:08:45.820 --> 00:08:50.139 have the same success. Yeah, yeah. This is a 00:08:50.139 --> 00:08:53.500 great opportunity, I think. Lookalore, it seems 00:08:53.500 --> 00:08:55.940 like it might be one of those low -risk, high 00:08:55.940 --> 00:09:00.840 -reward type of things as well, meaning if somebody 00:09:00.840 --> 00:09:03.360 uses it and if it doesn't work, then there's 00:09:03.360 --> 00:09:07.070 not a really bad side effect. Is that pretty 00:09:07.070 --> 00:09:12.490 accurate? Yeah. I mean, so it's a type of folate, 00:09:12.590 --> 00:09:15.490 and we know folates are pretty safe long term. 00:09:15.789 --> 00:09:20.129 They're natural vitamins. And one of the great 00:09:20.129 --> 00:09:24.409 things about B vitamins, so folate is vitamin 00:09:24.409 --> 00:09:28.169 B9. And so the B vitamins in general are what 00:09:28.169 --> 00:09:32.049 we call water soluble. which means you pee them 00:09:32.049 --> 00:09:34.990 out at the end of the day. So your body has a 00:09:34.990 --> 00:09:38.289 natural mechanism for controlling, you know, 00:09:38.289 --> 00:09:41.649 how much you have. So, you know, so that's really 00:09:41.649 --> 00:09:46.090 good. And so the worst thing you do, what we 00:09:46.090 --> 00:09:48.070 say is the worst thing you do is make expensive 00:09:48.070 --> 00:09:55.129 pee. Okay. Okay. I've heard that with like bodybuilders 00:09:55.129 --> 00:09:58.049 and people would take vitamins and supplements 00:09:58.049 --> 00:10:01.350 and so forth. Some people will just say it's 00:10:01.350 --> 00:10:04.029 just expensive pee and so forth. So I like that. 00:10:04.210 --> 00:10:08.870 No, it's kind of like a Intranasal oxytocin is 00:10:08.870 --> 00:10:11.350 kind of like that too with autism But it doesn't 00:10:11.350 --> 00:10:13.710 have great success and it seems like the look 00:10:13.710 --> 00:10:19.230 of Warren has better success Can you just start 00:10:19.230 --> 00:10:22.710 with how? You discover look of Warren as a possible 00:10:22.710 --> 00:10:26.289 treatment option for autism Sure, you know, I'll 00:10:26.289 --> 00:10:28.789 briefly kind of tell you guys that the story 00:10:28.990 --> 00:10:35.769 you know, of the discovery kind of of of leukovorin 00:10:35.769 --> 00:10:38.269 as a treatment because it's kind of interesting. 00:10:39.470 --> 00:10:44.690 So what we know, not to start out technical, 00:10:45.230 --> 00:10:48.769 but what we can see here is a brain and this 00:10:48.769 --> 00:10:51.330 was of course we know is important. This controls 00:10:51.330 --> 00:10:54.409 how we think and how we move, but to get into 00:10:54.409 --> 00:10:56.629 the brain everything that goes into the brain 00:10:56.970 --> 00:11:01.629 has to be actually selected to go in there because 00:11:01.629 --> 00:11:04.690 the brain is a very, very controlled environment. 00:11:05.730 --> 00:11:07.830 So we have this thing called the blood -brain 00:11:07.830 --> 00:11:09.909 barrier. When you have your blood over here, 00:11:10.029 --> 00:11:13.929 these are your red cells, going through your 00:11:13.929 --> 00:11:17.190 vessels, things can't just go into the brain. 00:11:17.870 --> 00:11:20.950 There's this barrier here that selects all the 00:11:20.950 --> 00:11:23.889 molecules that actually go in there. And so that's 00:11:23.889 --> 00:11:28.679 a good and bad thing, right? You know, that if 00:11:28.679 --> 00:11:33.299 you don't get things in there that are not supposed 00:11:33.299 --> 00:11:37.259 to be in there, but the other side of it is that 00:11:37.259 --> 00:11:39.659 you have to have these special carriers to bring 00:11:39.659 --> 00:11:41.440 things into the brain. If they weren't working, 00:11:42.179 --> 00:11:44.940 you know, that's a problem. You know, you don't 00:11:44.940 --> 00:11:48.659 get what you need into the brain. So one of the 00:11:48.659 --> 00:11:50.519 things that we know that is really important 00:11:50.519 --> 00:11:55.279 is folate. Okay, and many people think of folate 00:11:55.279 --> 00:11:58.200 five, methyl tetrahydrofolate is kind of our 00:11:58.200 --> 00:12:01.940 main folate in our body. And so that has to be 00:12:01.940 --> 00:12:04.659 brought into the brain. And there's really specialized 00:12:04.659 --> 00:12:07.279 mechanisms. You know, the body is very complex. 00:12:08.279 --> 00:12:10.360 So there's this thing called the folate receptor 00:12:10.360 --> 00:12:13.279 alpha, which you can see here. And here's the 00:12:13.279 --> 00:12:16.100 blood vessel here. And here's the brain, the 00:12:16.100 --> 00:12:20.379 cerebral spinal fluid. And so this receptor, 00:12:20.679 --> 00:12:24.820 actually binds onto folate and it pulls it across 00:12:24.820 --> 00:12:31.480 and dumps it into the brain. And this is really 00:12:31.480 --> 00:12:35.019 important because the amount of folate in the 00:12:35.019 --> 00:12:38.320 brain, the concentration, is two to three times 00:12:38.320 --> 00:12:42.620 higher than it is in the blood. So this is actually 00:12:42.620 --> 00:12:45.120 doing work and pulling folate into the brain 00:12:45.120 --> 00:12:48.500 and dumping it from the vessels into the brain. 00:12:48.759 --> 00:12:52.200 in doing a lot of work. There's other ways of 00:12:52.200 --> 00:12:54.340 getting folate into the brain. We have something 00:12:54.340 --> 00:12:56.740 called the reduced folate carrier over here, 00:12:57.019 --> 00:12:59.820 but you can see that it's smaller than the folate 00:12:59.820 --> 00:13:02.279 receptor alpha, and there's a reason for it. 00:13:02.279 --> 00:13:05.860 It just doesn't like folate as much. You know, 00:13:05.860 --> 00:13:07.860 you could think of the folate receptor alpha 00:13:07.860 --> 00:13:12.600 as kind of a fire hose and the reduced folate 00:13:12.600 --> 00:13:17.759 carrier as a straw. So we really want this to 00:13:17.759 --> 00:13:23.409 work. Well, so we know folate is really, really, 00:13:23.409 --> 00:13:29.929 really important. And so really folate is one 00:13:29.929 --> 00:13:33.929 of the most important vitamins for a number of 00:13:33.929 --> 00:13:36.690 different reasons. We have something called the 00:13:36.690 --> 00:13:41.289 folate cycle, which is here. And it does a number 00:13:41.289 --> 00:13:43.429 of things. It processes folate in a number of 00:13:43.429 --> 00:13:47.600 ways for the body. You know, first you have the 00:13:47.600 --> 00:13:53.299 stuff on the left -hand side, and that is where 00:13:53.299 --> 00:13:56.559 folate makes something called purines. And those 00:13:56.559 --> 00:14:04.519 are the building blocks of certain genetic material, 00:14:04.700 --> 00:14:08.279 RNA and DNA. So we know if you don't have folate, 00:14:08.419 --> 00:14:12.159 you're not going to make RNA and DNA well, and 00:14:12.159 --> 00:14:15.440 that's our genetic code. so you actually can 00:14:15.440 --> 00:14:18.659 get genetic abnormalities if you don't have folate 00:14:18.659 --> 00:14:23.100 available. Folate is also important for making 00:14:23.100 --> 00:14:26.240 something called BH4, or tetrahydrobiopterin, 00:14:26.419 --> 00:14:29.840 and that's really important for making neurotransmitters, 00:14:30.179 --> 00:14:32.940 serotonin, melatonin, dopamine, norepinephrine, 00:14:33.639 --> 00:14:39.590 and for nitric oxide production. And there's 00:14:39.590 --> 00:14:43.309 a really interesting phenomenon with BH4 and 00:14:43.309 --> 00:14:46.549 why it's so important. And that is for nitric 00:14:46.549 --> 00:14:50.169 oxide, we've heard good and bad things about 00:14:50.169 --> 00:14:53.230 nitric oxide. Some people say it's toxic, some 00:14:53.230 --> 00:14:56.129 people say it's good. Well, for the most part, 00:14:56.210 --> 00:14:59.169 it's a good molecule in our body. But one of 00:14:59.169 --> 00:15:02.590 the things that happens is if you don't have 00:15:02.590 --> 00:15:06.789 BH4, when it's being made, instead of making 00:15:06.789 --> 00:15:10.820 nitric oxide, you actually make a toxic molecule 00:15:10.820 --> 00:15:20.899 called a p -oxynitrate. So the same pathway that 00:15:20.899 --> 00:15:24.340 produces nitric oxide, when you don't have BH4, 00:15:24.360 --> 00:15:27.320 which it needs for nitric oxide production, it 00:15:27.320 --> 00:15:30.240 ends up it doesn't stop. It keeps trying to make 00:15:30.240 --> 00:15:32.820 nitric oxide, but if you don't have BH4, it actually 00:15:32.820 --> 00:15:37.580 makes a toxic molecule. So BH4 is extremely important. 00:15:37.799 --> 00:15:39.860 And then it's important for something called 00:15:39.860 --> 00:15:42.279 ATP, which is important for the mitochondria, 00:15:42.559 --> 00:15:46.139 the powerhouse of our cell to make energy. And 00:15:46.139 --> 00:15:50.940 ATP is the energy currency of ourselves. On the 00:15:50.940 --> 00:15:52.960 other side is what a lot of people talk about 00:15:52.960 --> 00:15:58.159 is methylation. And so on the other side of the 00:15:58.159 --> 00:16:00.419 folate cycle, you have methylation, where you 00:16:00.419 --> 00:16:04.720 use B12 and folate. to make methyl groups, and 00:16:04.720 --> 00:16:09.399 those are important molecules that regulate if 00:16:09.399 --> 00:16:13.360 DNA is turned on and off. So that's really important, 00:16:13.899 --> 00:16:17.299 right? Every cell in your body has the same DNA. 00:16:17.559 --> 00:16:20.600 So how do the cells work differently? Well, it's 00:16:20.600 --> 00:16:23.980 because in certain cells the DNA is turned on 00:16:23.980 --> 00:16:27.120 or off, and that's all due to methylation. So 00:16:27.120 --> 00:16:29.620 if methylation isn't working, you're in trouble. 00:16:33.039 --> 00:16:36.720 And it ends up that this then goes into what 00:16:36.720 --> 00:16:39.960 we call redox metabolism or trans -sulfuration 00:16:39.960 --> 00:16:43.200 to make glutathione, which is your major antioxidant 00:16:43.200 --> 00:16:46.279 of your body. So you can see folate is really 00:16:46.279 --> 00:16:49.799 central to all of these different things. Some 00:16:49.799 --> 00:16:54.200 of the nuances here is that we have the MTHFR. 00:16:54.840 --> 00:16:57.799 And a lot of people like to talk about the polymorphisms, 00:16:58.320 --> 00:17:02.000 that is small changes that make it make it more 00:17:02.000 --> 00:17:05.019 or less efficient. And so it may be more or less 00:17:05.019 --> 00:17:08.380 efficient at making 5 -methyltetrahydrofolate, 00:17:08.440 --> 00:17:13.940 which we think of as our main folate. And then 00:17:13.940 --> 00:17:19.059 that will interfere with methylation. But you 00:17:19.059 --> 00:17:21.079 also have to realize that we need folate over 00:17:21.079 --> 00:17:25.460 here. This is 5 -10 -formaline folate. That's 00:17:25.460 --> 00:17:30.029 what leukovorin comes in. And that goes to this 00:17:30.029 --> 00:17:35.130 other side. So it's a very complex pathway. The 00:17:35.130 --> 00:17:38.230 great thing about leukovorin and folinic acid 00:17:38.230 --> 00:17:42.529 is that the gut actually turns half of what's 00:17:42.529 --> 00:17:45.049 made of leukovorin when you take it orally to 00:17:45.049 --> 00:17:48.250 five -method tetrahydrofolate. So you actually 00:17:48.250 --> 00:17:50.890 have folate come in here and over here. So you 00:17:50.890 --> 00:17:55.650 kind of bypass the MTHFR, which is a good thing 00:17:55.650 --> 00:17:59.730 if it's not working all that well. The other 00:17:59.730 --> 00:18:03.109 really important thing, concept in folate, is 00:18:03.109 --> 00:18:07.029 that folic acid, which we all know of, we think 00:18:07.029 --> 00:18:12.269 that that's our great type of folate, is a synthetic 00:18:12.269 --> 00:18:15.849 form of folate. It's not natural. So our body 00:18:15.849 --> 00:18:19.829 can't use it naturally. And it has to go through 00:18:19.829 --> 00:18:22.089 something called the dihydrofolate reductase 00:18:22.089 --> 00:18:28.119 enzyme to change it from... folic acid into tetrahydrofolate 00:18:28.119 --> 00:18:31.519 for it to be used. And there's two problems there. 00:18:31.579 --> 00:18:36.779 One, some people have changes in the dihydrofolate 00:18:36.779 --> 00:18:40.420 reductase enzyme that makes it less efficient. 00:18:41.079 --> 00:18:46.079 And two, we only have so many of these. So the 00:18:46.079 --> 00:18:49.279 idea of giving more folic acid, right, you want 00:18:49.279 --> 00:18:50.880 to get more folate in the body, you say, I'll 00:18:50.880 --> 00:18:54.140 just give more folic acid. But you can't do that. 00:18:54.200 --> 00:18:56.640 because there's a limitation here, right? There's 00:18:56.640 --> 00:19:00.660 a bottleneck because you only have so much of 00:19:00.660 --> 00:19:04.279 this enzyme, so you only can change so much folic 00:19:04.279 --> 00:19:07.859 acid into tetrahydrofolate. So these are just 00:19:07.859 --> 00:19:10.640 some of the nuances of folate to think about. 00:19:11.440 --> 00:19:15.940 So sorry to go on. No, that's fine. I was going 00:19:15.940 --> 00:19:20.720 to ask you about BH4. I had it on my notes here. 00:19:21.000 --> 00:19:25.779 I'm glad you brought it up. Did you have other 00:19:25.779 --> 00:19:30.240 questions or? No, I just, um, I ran into it, 00:19:30.240 --> 00:19:35.660 um, covering, um, the womb and like the development 00:19:35.660 --> 00:19:38.339 process of the womb and like the timing and so 00:19:38.339 --> 00:19:42.140 forth. And I ran into VH4 and I was connected 00:19:42.140 --> 00:19:45.859 to intellectual disabilities and motor movements, 00:19:46.339 --> 00:19:48.799 especially gross motor and things like seizures. 00:19:50.079 --> 00:19:52.660 And I was just like, I bet this is involved. 00:19:53.039 --> 00:19:58.900 But you confirmed that, so. Yeah, the major disorders 00:19:58.900 --> 00:20:05.420 that of lack of BH4, usually a person looks like 00:20:05.420 --> 00:20:09.359 a Parkinson patient. So the syndromes called 00:20:09.359 --> 00:20:12.880 Sagawa syndrome or dopamine response of dystonia. 00:20:13.659 --> 00:20:17.440 The major symptoms you see is more like a Parkinson's 00:20:17.440 --> 00:20:19.779 patient, but there's other things too, because 00:20:19.779 --> 00:20:22.220 it's not only dopamine that you've lost, you've 00:20:22.220 --> 00:20:26.460 lost serotonin and norepinephrine. It's really, 00:20:26.460 --> 00:20:33.140 really important. Yeah. With the placenta and 00:20:33.140 --> 00:20:36.740 neurogenesis, I found that it was important with 00:20:36.740 --> 00:20:41.079 that fetal ATP that you show. Yeah, so it's very 00:20:41.079 --> 00:20:45.579 important. It's a hard molecule to study because 00:20:45.579 --> 00:20:48.420 it's a fleeting molecule. It's not very stable. 00:20:49.059 --> 00:20:51.339 And then it's very expensive as a supplement. 00:20:52.359 --> 00:20:55.160 We used to be able to get some from Switzerland, 00:20:55.240 --> 00:20:58.819 but I don't think they make it anymore. And so 00:20:58.819 --> 00:21:01.500 now, that's where I originally started, was studying 00:21:01.500 --> 00:21:06.380 BH4. And there's a medicine called KuVan, which 00:21:06.380 --> 00:21:11.970 is synthetic BH4. And it's made for a rare type 00:21:11.970 --> 00:21:17.250 of phenylalanemia. And since it's a rare disease, 00:21:17.349 --> 00:21:21.470 it's extremely expensive. So it's not a practical 00:21:21.470 --> 00:21:26.809 thing to use. But in our studies, we show that 00:21:26.809 --> 00:21:30.109 it does help somewhat. But folate helps a lot 00:21:30.109 --> 00:21:37.250 more. OK, yeah, yeah. To get back to the cerebral 00:21:37.250 --> 00:21:42.150 folate deficiency story, we have to thank Dr. 00:21:42.390 --> 00:21:46.809 Vincent Raymakers. He's a pediatric neurologist 00:21:46.809 --> 00:21:49.670 from Belgium and he was working in Germany at 00:21:49.670 --> 00:21:54.289 that time. He was seeing all these patients that 00:21:54.289 --> 00:21:56.410 had neurodevelopmental disorders and he couldn't 00:21:56.410 --> 00:22:01.349 figure out what was going on with them, why they 00:22:01.349 --> 00:22:04.740 had the disorders. worked them up. And then he 00:22:04.740 --> 00:22:10.079 teamed up with Dr. Blau, who's in Zurich, Switzerland. 00:22:11.279 --> 00:22:15.039 And Dr. Blau is probably the most world renowned 00:22:15.039 --> 00:22:18.500 scientist on the neurochemistry of the brain. 00:22:19.960 --> 00:22:24.859 And so what he would do is he sent samples of 00:22:25.900 --> 00:22:28.740 cerebral spinal fluid so he did some LPs this 00:22:28.740 --> 00:22:31.319 is what happens if we can't figure it out we 00:22:31.319 --> 00:22:33.539 try to do everything and one of them is to take 00:22:33.539 --> 00:22:36.660 some fluid from the CSF the fluid that surrounds 00:22:36.660 --> 00:22:38.700 the brain and analyze it and say is there something 00:22:38.700 --> 00:22:42.579 there or something not there and they discovered 00:22:42.579 --> 00:22:47.500 that these patients had very low folate in their 00:22:47.500 --> 00:22:51.240 brain and so this is kind of a new discovery. 00:22:52.860 --> 00:22:55.839 And you can see that he studied these children 00:22:55.839 --> 00:22:58.579 over time. And what was interesting is when he 00:22:58.579 --> 00:23:00.819 looked at some folate levels, they actually dropped 00:23:00.819 --> 00:23:06.960 over time in some of these kids. So one of the 00:23:06.960 --> 00:23:12.339 things that he did was he wanted to know why 00:23:12.339 --> 00:23:15.039 this was. So he knew that the folate receptor 00:23:15.039 --> 00:23:19.619 alpha was the major transport mechanism. So of 00:23:19.619 --> 00:23:21.900 course he said, oh, this must be a genetic problem. 00:23:22.200 --> 00:23:25.559 with the folate receptor alpha. So he sequenced 00:23:25.559 --> 00:23:28.819 the gene, but he couldn't find any abnormalities. 00:23:30.980 --> 00:23:33.519 And, and so he said, you know, it's kind of scratchy 00:23:33.519 --> 00:23:38.759 sentence, huh? So then what happened is he teamed 00:23:38.759 --> 00:23:41.900 up at the same time. It's an interesting story. 00:23:42.339 --> 00:23:49.460 At the same time, Dr. Quatro's at SUNY downstate 00:23:49.460 --> 00:23:52.890 in Brooklyn, New York, was looking at folate, 00:23:53.049 --> 00:23:58.170 but for birth defects. And trying to figure out 00:23:58.170 --> 00:24:02.130 why, you know, we didn't get folate into the 00:24:02.130 --> 00:24:05.309 baby and they caused birth defects. And what 00:24:05.309 --> 00:24:07.769 he discovered, at the same time he was looking 00:24:07.769 --> 00:24:12.529 at birth defects, and he discovered that in these 00:24:12.529 --> 00:24:16.289 transport mechanisms, that there were these two 00:24:16.289 --> 00:24:20.519 antibodies running around people's bloods. Usually, 00:24:21.140 --> 00:24:26.279 antibodies attack viruses and bacteria to protect 00:24:26.279 --> 00:24:29.599 us. But some people have antibodies to themselves, 00:24:29.700 --> 00:24:32.160 to their own body, and so -called autoimmune 00:24:32.160 --> 00:24:36.559 diseases. So he found that there was these antibodies 00:24:36.559 --> 00:24:40.140 that bound to this folate receptor alpha here 00:24:40.140 --> 00:24:44.960 and stopped it from working. So he was looking 00:24:44.960 --> 00:24:49.799 at birth defects and And Dr. Rainmaker's found 00:24:49.799 --> 00:24:53.380 these patients. So Dr. Rainmaker said, well, 00:24:53.380 --> 00:24:57.119 why don't we test these kiddos for these antibodies? 00:24:58.000 --> 00:25:00.400 And so then they published their findings, really, 00:25:00.559 --> 00:25:03.319 in a really nice paper in the New England Journal 00:25:03.319 --> 00:25:06.339 of Medicine, probably the best journal in the 00:25:06.339 --> 00:25:10.660 world, to describe this new phenomenon called 00:25:10.660 --> 00:25:14.779 cerebral folate deficiency. And they found that 00:25:14.779 --> 00:25:20.609 these kiddos had particular symptoms. Starting 00:25:20.609 --> 00:25:24.970 usually before year olds, they'd have decreasing 00:25:24.970 --> 00:25:27.910 head growth, so their brain stopped growing, 00:25:28.009 --> 00:25:32.230 so their head stopped growing. They'd have neurodevelopmental 00:25:32.230 --> 00:25:34.710 regressions, so they'd lose skills that they 00:25:34.710 --> 00:25:38.750 had. They'd have dyskinesias, which are movement 00:25:38.750 --> 00:25:44.099 disorders. Some of them had epilepsy. And then 00:25:44.099 --> 00:25:46.119 some of them had what we call periminal signs, 00:25:46.240 --> 00:25:50.799 which looks like cerebral palsy. And if they 00:25:50.799 --> 00:25:53.240 weren't treated, they went on to have visual 00:25:53.240 --> 00:26:00.299 disturbances and hearing loss. So these kids, 00:26:00.720 --> 00:26:03.119 they measured this antibody, this folate receptor 00:26:03.119 --> 00:26:05.940 antibody, and looked at the titers. And we can 00:26:05.940 --> 00:26:08.359 see that the mean titers in the patients with 00:26:08.359 --> 00:26:11.299 cerebral folate deficiency were all the way up 00:26:11.299 --> 00:26:14.509 here. where the control subjects were down here. 00:26:16.490 --> 00:26:19.549 So the question was, OK, well, how do we treat 00:26:19.549 --> 00:26:24.670 this? Well, they had also used leukovorin. So 00:26:24.670 --> 00:26:28.049 that's what we'll talk about a little bit. And 00:26:28.049 --> 00:26:32.190 the thing about leukovorin is some of it gets 00:26:32.190 --> 00:26:36.430 turned into 5 -methy tetrahydrofolate. But leukovorin 00:26:36.430 --> 00:26:40.250 is a reduced folate like 5 -methy tetrahydrofolate. 00:26:40.519 --> 00:26:43.460 and it can go through this reduced folate carrier 00:26:43.460 --> 00:26:47.460 and get and go into the brain. Now of course 00:26:47.460 --> 00:26:50.079 it's not that easy remember I said that reduced 00:26:50.079 --> 00:26:53.500 folate carrier is like a straw and the levels 00:26:53.500 --> 00:26:56.279 in the brain are two to three times out of the 00:26:56.279 --> 00:26:59.940 blood normally. So what you have to do is get 00:26:59.940 --> 00:27:04.380 high doses of folate in the blood and push it 00:27:04.380 --> 00:27:13.450 through the straw to the other side. And so some 00:27:13.450 --> 00:27:18.009 of the science that we looked at is, okay, we 00:27:18.009 --> 00:27:20.549 know that we have these folate antibodies. Do 00:27:20.549 --> 00:27:24.190 they correlate with levels of folate in the cerebral 00:27:24.190 --> 00:27:27.769 spinal fluid? So that's a question people ask. 00:27:27.829 --> 00:27:29.809 How do you know that they really are doing something? 00:27:30.210 --> 00:27:32.849 So this is a study by Dr. Rainmakers where he 00:27:32.849 --> 00:27:35.509 showed that the blocking antibody correlated 00:27:35.509 --> 00:27:39.109 with levels of. folate in the CSF, so we know 00:27:39.109 --> 00:27:41.789 that correlates. And this is a study we did on 00:27:41.789 --> 00:27:44.690 autism where we found that there was a correlation. 00:27:45.289 --> 00:27:48.410 Although in autism it's very interesting, we 00:27:48.410 --> 00:27:52.029 didn't find any of them were below the normal 00:27:52.029 --> 00:27:55.069 limit. We found a lot of them were low normal 00:27:55.069 --> 00:27:59.529 but not below the normal limit. And so there's 00:27:59.529 --> 00:28:04.170 some subtleties in autism that we think are driving 00:28:04.170 --> 00:28:11.700 many things. So as more so they first described 00:28:11.700 --> 00:28:16.339 this These patients in the New England Journal 00:28:16.339 --> 00:28:19.700 of Medicine and then other papers started to 00:28:19.700 --> 00:28:24.059 be Published and so this one was cerebral folate 00:28:24.059 --> 00:28:28.440 deficiency with autism and the response to phalamic 00:28:28.440 --> 00:28:32.099 acid You know, so they show that you can use 00:28:32.099 --> 00:28:36.460 phalamic acid to improve symptoms, and they described 00:28:36.460 --> 00:28:40.740 an individual with autism. So, and then another 00:28:40.740 --> 00:28:43.980 report came along of autistic symptoms, developmental 00:28:43.980 --> 00:28:46.980 regression, mental retardation, epilepsy, and 00:28:46.980 --> 00:28:50.440 dyskinesia in full deficiency. But again, started, 00:28:50.680 --> 00:28:53.619 we started to realize that, oh, there's patients, 00:28:53.720 --> 00:28:58.180 one of the phenotypes of this is autism. And 00:28:58.180 --> 00:29:01.599 so, and here's another one where they found low 00:29:01.599 --> 00:29:06.039 functioning kids. with autism had a cerebral 00:29:06.039 --> 00:29:11.099 folate deficiency. And this is an interesting, 00:29:11.920 --> 00:29:14.559 in one of their studies, they looked at the folate 00:29:14.559 --> 00:29:17.740 antibody titer and they looked at aggressive 00:29:17.740 --> 00:29:22.359 behavior. And you can see that aggressive behavior 00:29:22.359 --> 00:29:29.299 matches the titer almost exactly. Wow. So then, 00:29:29.339 --> 00:29:32.019 of course, we wanted to know more about treatment. 00:29:32.099 --> 00:29:36.059 So this is a paper that Dr. Rainmakers did to 00:29:36.059 --> 00:29:40.579 show if you start treatment, how many people 00:29:40.579 --> 00:29:44.960 recover from these different symptoms. And things 00:29:44.960 --> 00:29:47.880 like periminal tract defects, motor problems, 00:29:48.480 --> 00:29:55.279 unsteadiness, very much dyskinesia, so -so. and 00:29:55.279 --> 00:30:00.220 he found that autism and intellectual disability 00:30:00.220 --> 00:30:03.339 not so much. You really had to start early in 00:30:03.339 --> 00:30:11.220 treatment. So then they also linked cerebral 00:30:11.220 --> 00:30:14.000 folate deficiency to mitochondrial disorders. 00:30:14.500 --> 00:30:17.519 Because you remember, I said the folate receptor 00:30:17.519 --> 00:30:21.180 alpha has to essentially pull folate into the 00:30:21.180 --> 00:30:25.579 nervous system. So it takes energy. And so if 00:30:25.579 --> 00:30:28.619 the mitochondria isn't working, it's not gonna 00:30:28.619 --> 00:30:32.099 work. But this is an outstanding study because 00:30:32.099 --> 00:30:35.519 what Dr. Rainmaker showed was this is the patient 00:30:35.519 --> 00:30:39.019 that started when they were diagnosed and the 00:30:39.019 --> 00:30:42.059 left. And so these are MRIs and you don't have 00:30:42.059 --> 00:30:44.980 to be a neuroradiologist to see that there's 00:30:44.980 --> 00:30:47.619 a really bad MRI because all this white stuff 00:30:47.619 --> 00:30:51.240 does not belong there. So that's loss of white 00:30:51.240 --> 00:30:55.519 matter. the wires that are in the brain. So it 00:30:55.519 --> 00:30:57.460 looks very severe and you can see almost these 00:30:57.460 --> 00:31:01.880 holes inside the thalamus and basal ganglias. 00:31:03.259 --> 00:31:05.819 So most of the time we would say, oh, this is 00:31:05.819 --> 00:31:09.160 not a recoverable brain. But after three years 00:31:09.160 --> 00:31:11.900 of treatment with some mitochondrial supplements 00:31:11.900 --> 00:31:15.579 and leukovorin, the brain is almost back to normal. 00:31:17.160 --> 00:31:23.190 Wow. So that's pretty impressive. So going on 00:31:23.190 --> 00:31:25.089 with the mitochondrial disease, then another 00:31:25.089 --> 00:31:30.089 paper came out where they found that there was 00:31:30.089 --> 00:31:32.910 a whole slew of patients with mitochondrial disease 00:31:32.910 --> 00:31:37.849 that had cerebral folate deficiency. So, you 00:31:37.849 --> 00:31:41.009 know, the story started building. So what happened 00:31:41.009 --> 00:31:44.329 is, you know, myself and so this is about 2008. 00:31:44.529 --> 00:31:47.369 And so and this is when I was just starting to 00:31:47.369 --> 00:31:52.619 really treat kids with autism. And so I was working 00:31:52.619 --> 00:31:55.299 with Dr. Rossignol. We were working on some review 00:31:55.299 --> 00:31:59.160 papers and we said, well, kids with autism have 00:31:59.160 --> 00:32:01.920 mitochondrial problems. You know, they have immune 00:32:01.920 --> 00:32:05.740 problems. How many of these kids are running 00:32:05.740 --> 00:32:08.539 around our clinic with this folate receptor antibody? 00:32:10.220 --> 00:32:11.839 He said, you know, we can measure it. We could 00:32:11.839 --> 00:32:15.190 send it to Dr. Quatros. And so what we did is 00:32:15.190 --> 00:32:18.490 we systematically offered the test to our patients 00:32:18.490 --> 00:32:23.569 when they came in. And we made an interesting 00:32:23.569 --> 00:32:28.690 discovery which we published in 2012 in molecular 00:32:28.690 --> 00:32:32.490 psychiatry of the cerebral folate antibodies 00:32:32.490 --> 00:32:39.829 in autism. And what we discovered was that of 00:32:39.829 --> 00:32:44.140 the blocking antibody, 60 % of the kiddos had 00:32:44.140 --> 00:32:47.460 the blocking antibody and 50 % had the binding 00:32:47.460 --> 00:32:51.400 antibody. So it wasn't subtle. And if you ask 00:32:51.400 --> 00:32:56.240 how many had either antibody, 75 % had at least 00:32:56.240 --> 00:32:59.920 one or two antibodies. So that's a lot of kids 00:32:59.920 --> 00:33:07.740 with autism. And so, you know, of course we didn't 00:33:07.740 --> 00:33:10.980 have controls to see if it was, you know, higher 00:33:10.980 --> 00:33:15.309 than control. So Dr. Ray Maker had another study 00:33:15.309 --> 00:33:18.250 where he compared the percentage of kids with 00:33:18.250 --> 00:33:21.690 autism with the antibodies to controls, which 00:33:21.690 --> 00:33:24.069 were developmentally delayed controls without 00:33:24.069 --> 00:33:27.609 autism. And we can see in his study, 47 % of 00:33:27.609 --> 00:33:31.269 them had the antibody, only 3 % of the kids with 00:33:31.269 --> 00:33:34.910 developmental delays, but no autism had the antibodies. 00:33:35.609 --> 00:33:38.369 That really discriminates the autism out of it. 00:33:39.450 --> 00:33:44.250 It extracts it out. And so then another study 00:33:44.250 --> 00:33:51.769 was done by at the NIH by Susan Suito with measure 00:33:51.769 --> 00:33:55.569 using LPs to measure, you know, folate in the 00:33:55.569 --> 00:33:59.470 CSF of kids with autism. And so what she found 00:33:59.470 --> 00:34:02.869 is that if you measure the kids that have frankly 00:34:02.869 --> 00:34:08.489 low CSF levels, it's 18%. So at least 18 % have 00:34:08.489 --> 00:34:13.090 frankly low levels of folates are below normal. 00:34:13.510 --> 00:34:15.570 But if you remember, when I showed you that other 00:34:15.570 --> 00:34:17.849 diagram, I said in our study, we found that these 00:34:17.849 --> 00:34:20.250 kids had kind of more low normal. So this doesn't 00:34:20.250 --> 00:34:22.289 even kids the kids that are low normal. So those 00:34:22.289 --> 00:34:25.070 that have clearly defined cerebral folate deficiency 00:34:25.070 --> 00:34:29.230 is 18%, which is a big number, you know, that's, 00:34:29.269 --> 00:34:32.429 you know, a fifth of kids with autism, you know. 00:34:33.869 --> 00:34:39.639 So, so one of the things we said is, well, If 00:34:39.639 --> 00:34:43.360 the kids have the antibody, do you think that 00:34:43.360 --> 00:34:46.380 they will respond to treatment? We knew about 00:34:46.380 --> 00:34:50.260 leukovorin. So what we did is the kids that were 00:34:50.260 --> 00:34:54.860 positive, 44 of them, we treated with leukovorin, 00:34:55.219 --> 00:34:58.739 two milligrams per kilogram. And this was open 00:34:58.739 --> 00:35:00.840 label, so they knew they were getting it. And 00:35:00.840 --> 00:35:03.019 then we compare them to something called a weightless 00:35:03.019 --> 00:35:07.809 control group. And these were kiddos. that were 00:35:07.809 --> 00:35:13.670 essentially waiting for results. And neither 00:35:13.670 --> 00:35:16.269 of them made any other changes. And when they 00:35:16.269 --> 00:35:19.409 came back to the clinic, we asked them to rate 00:35:19.409 --> 00:35:24.650 whether things got better or worse on several 00:35:24.650 --> 00:35:27.369 different aspects. But the most important ones 00:35:27.369 --> 00:35:32.039 were language and behavior. And what we found 00:35:32.039 --> 00:35:34.219 is that in all the language measures, receptive 00:35:34.219 --> 00:35:37.360 language, expressive language, and verbal communication, 00:35:38.139 --> 00:35:43.000 there was improvement. So higher up is improvement. 00:35:43.039 --> 00:35:45.239 So you can see the black dots are the ones that 00:35:45.239 --> 00:35:47.880 were treated. So you could just see, you don't 00:35:47.880 --> 00:35:50.760 even need statistics to see that there's more 00:35:50.760 --> 00:35:54.199 black dots above the line here than there are 00:35:54.199 --> 00:35:59.420 clear dots. We also found that improved stereotype 00:35:59.420 --> 00:36:04.219 behavior. attention and if you look at who improved 00:36:04.219 --> 00:36:08.679 you say those that improved in receptive language 00:36:08.679 --> 00:36:14.179 about 66 percent 67 percent improved in expressive 00:36:14.179 --> 00:36:17.000 language receptive language and verbal communication 00:36:17.000 --> 00:36:21.639 in about a little less 40 percent improved on 00:36:21.639 --> 00:36:24.780 verbal communication but attention improved in 00:36:24.780 --> 00:36:30.139 about 60 percent mood about 50 % stereotype behavior 00:36:30.139 --> 00:36:33.360 about 50 % so it wasn't everybody but it's a 00:36:33.360 --> 00:36:37.500 substantial number so then you know so we said 00:36:37.500 --> 00:36:40.019 wow this is really interesting and a potential 00:36:40.019 --> 00:36:43.019 treatment but of course what we did first was 00:36:43.019 --> 00:36:45.719 something called an open label study and open 00:36:45.719 --> 00:36:48.079 label study means people know that they're getting 00:36:48.079 --> 00:36:50.500 the drugs so they're biased right they say oh 00:36:50.500 --> 00:36:53.679 yeah this this thing worked yeah I love this 00:36:53.679 --> 00:36:58.550 so we had to do the double blind placebo control 00:36:58.550 --> 00:37:01.889 study. And at this time, I was at when we did 00:37:01.889 --> 00:37:07.110 this study, we were I was at UT Houston. And 00:37:07.110 --> 00:37:10.010 they just got recruited to Arkansas Children's 00:37:10.010 --> 00:37:12.829 Hospital to lead their autism program. So I said, 00:37:12.849 --> 00:37:15.070 Well, the first thing I'm going to do is do a 00:37:15.070 --> 00:37:19.150 controlled study on leukovorin. And that study 00:37:19.150 --> 00:37:25.889 was published in 2016. And what we did is we 00:37:25.889 --> 00:37:29.309 randomized kids, 48 kids, to either see if you 00:37:29.309 --> 00:37:32.710 see a placebo or leucovorin. At that time, we 00:37:32.710 --> 00:37:35.710 were calling it high -dose folinic acid. We don't 00:37:35.710 --> 00:37:38.949 like using folinic acid anymore because so many 00:37:38.949 --> 00:37:43.250 people confuse it with folic acid. So we've kind 00:37:43.250 --> 00:37:45.789 of changed just saying leucovorin, so there's 00:37:45.789 --> 00:37:48.769 no confusion. But it's essentially the same molecule. 00:37:50.250 --> 00:37:52.590 And so in the first, in our open -label study, 00:37:52.769 --> 00:37:55.389 we found that language was improving. So that 00:37:55.389 --> 00:37:59.530 was a great thing because what we could do is, 00:37:59.530 --> 00:38:02.909 you know, many problems that we have in studies 00:38:02.909 --> 00:38:09.429 of autism is that there isn't objective measures 00:38:09.429 --> 00:38:12.889 of improvement. Many of them are parent questionnaires 00:38:12.889 --> 00:38:15.070 or, you know, what does the physician think is 00:38:15.070 --> 00:38:18.150 better or is it not better, you know. But for 00:38:18.150 --> 00:38:26.570 language, you have very sophisticated measurement 00:38:26.570 --> 00:38:29.690 tools that can measure many aspects of language. 00:38:29.989 --> 00:38:31.809 And you can have somebody, a trained person, 00:38:31.829 --> 00:38:34.010 to actually do the measurement. And they don't 00:38:34.010 --> 00:38:36.369 know whether the child is on the medication or 00:38:36.369 --> 00:38:39.969 not. So we can actually put numbers to it. And 00:38:39.969 --> 00:38:42.610 so what we found is that you can see here in 00:38:42.610 --> 00:38:45.489 12 weeks, the ones that were in leucovore and 00:38:45.489 --> 00:38:48.719 ephelinic acid, their verbal communication increased 00:38:48.719 --> 00:38:52.079 dramatically compared to those that were on placebo 00:38:52.079 --> 00:38:54.539 and of course they were getting speech therapy 00:38:54.539 --> 00:38:56.539 and everything so they improved a little bit 00:38:56.539 --> 00:38:59.099 but you can see the difference here was dramatic. 00:38:59.880 --> 00:39:02.239 And then we asked a question because in this 00:39:02.239 --> 00:39:04.760 one we had all comers those that were positive 00:39:04.760 --> 00:39:07.840 and negative for the for the folate autoantibody 00:39:07.840 --> 00:39:11.179 and so we asked does it matter if you're positive 00:39:11.179 --> 00:39:14.380 or negative and we found that in fact it did 00:39:14.380 --> 00:39:19.820 and if you were positive for the folate autoantibody. 00:39:20.260 --> 00:39:23.360 If you had flenic acid or leukovorin, it was 00:39:23.360 --> 00:39:27.920 a 77 % response rate. And there's an important 00:39:27.920 --> 00:39:30.599 number called number needed to treat. So that's 00:39:30.599 --> 00:39:32.920 how many patients you have to treat to get one. 00:39:33.519 --> 00:39:35.739 And most people, right, you go to the doctor 00:39:35.739 --> 00:39:38.539 and you think that number should be one, right? 00:39:38.639 --> 00:39:40.420 You go to the doctor, they give you a drug, you're 00:39:40.420 --> 00:39:44.719 all better. So people will be survived surprised 00:39:44.719 --> 00:39:47.039 to find out in most clinical trials that number 00:39:47.039 --> 00:39:50.059 is anywhere from six to eight So you have to 00:39:50.059 --> 00:39:52.900 trade most medications. You have to treat six 00:39:52.900 --> 00:39:56.860 people just to get the effect that you want So 00:39:56.860 --> 00:40:00.059 a number of one point eight is very good and 00:40:00.059 --> 00:40:02.980 this is looking at a response criteria of you 00:40:02.980 --> 00:40:06.380 know a very Significant response to phallitic 00:40:06.380 --> 00:40:08.340 acid. Of course, there's other kids that have 00:40:08.340 --> 00:40:10.380 more of a lackluster response that are slower 00:40:10.639 --> 00:40:14.360 So this is pretty good. Now, what we did is we 00:40:14.360 --> 00:40:17.320 were able to equate it to how many hours of speech 00:40:17.320 --> 00:40:22.360 therapy this equals. It was 177 hours. So that 00:40:22.360 --> 00:40:26.420 would be three hours a week for a year, or about 00:40:26.420 --> 00:40:32.280 $7 ,000 worth of speech therapy for $300 worth 00:40:32.280 --> 00:40:37.070 of a drug. and you know it's not only important 00:40:37.070 --> 00:40:40.150 not trying to you know put down speech therapy 00:40:40.150 --> 00:40:42.909 but the fact is you know we were talking about 00:40:42.909 --> 00:40:46.610 this language is so so so important and the inability 00:40:46.610 --> 00:40:49.849 to communicate causes so many problems in children 00:40:49.849 --> 00:40:52.869 trying to recover and learn so it's just the 00:40:52.869 --> 00:40:55.409 fact if you can get them faster to the place 00:40:55.409 --> 00:40:58.090 they need to be they'll be in a lot better shape 00:40:58.090 --> 00:41:03.550 yeah and even even i think um the lack of language 00:41:04.010 --> 00:41:08.030 The inability to convey their needs is a big 00:41:08.030 --> 00:41:11.570 path for self -injurious behavior. I think that's 00:41:11.570 --> 00:41:13.969 what I do because they get frustrated. You're 00:41:13.969 --> 00:41:17.469 absolutely right. And that's what we're learning, 00:41:17.630 --> 00:41:19.630 right? With the spellers and such that there's 00:41:19.630 --> 00:41:24.130 stuff in there. Yeah, you can't get it out. And 00:41:24.130 --> 00:41:26.969 so it's very frustrating for them. So, you know, 00:41:26.969 --> 00:41:31.670 they can't tell you what they want to say. headbanging 00:41:31.670 --> 00:41:34.230 and stuff. So that's why language is so important. 00:41:34.250 --> 00:41:37.690 Now some people worry about when we start leukovorin, 00:41:37.750 --> 00:41:40.949 we get some hyperactivity sometimes in the initial 00:41:40.949 --> 00:41:44.789 few weeks. So we said, well, why don't we study 00:41:44.789 --> 00:41:47.630 this? Because in our clinical trial, every three 00:41:47.630 --> 00:41:50.429 weeks we asked about certain adverse effects 00:41:50.429 --> 00:41:53.409 specifically. And although we didn't ask about 00:41:53.409 --> 00:41:56.489 hyperactivity, we asked about agitation or excitement. 00:41:57.550 --> 00:42:00.989 And we can see at three weeks, those on leukovirin 00:42:00.989 --> 00:42:04.929 was about 20%. Those that are on placebo is about 00:42:04.929 --> 00:42:09.269 12%. By six weeks, they equaled each other at 00:42:09.269 --> 00:42:13.429 about 22%. And at nine weeks, and this is what 00:42:13.429 --> 00:42:16.429 we see at long -term that hyperactivity gets 00:42:16.429 --> 00:42:19.809 better, see at nine weeks, those on leukovirin 00:42:19.809 --> 00:42:23.909 plummeted to zero. Whereas the ones on placebo 00:42:23.909 --> 00:42:29.849 continued to have a higher rate. So, you know, 00:42:30.030 --> 00:42:32.030 scientifically you say, well, it's no different 00:42:32.030 --> 00:42:34.610 than placebo here if you look at statistics, 00:42:34.909 --> 00:42:38.449 but, you know, it does tell us that it's pretty 00:42:38.449 --> 00:42:41.630 much consistent with what you would see, you 00:42:41.630 --> 00:42:45.869 know, kind of in your normal daily routine and 00:42:45.869 --> 00:42:48.889 that with leukovorin eventually it does get better. 00:42:53.090 --> 00:42:58.840 So then the other really important aspect is 00:42:58.840 --> 00:43:02.340 the fact that going back, coming full circle 00:43:02.340 --> 00:43:07.880 to Dr. Quatro's research is that these same mechanisms 00:43:07.880 --> 00:43:11.000 with the folate autoantibody and the folate receptor 00:43:11.000 --> 00:43:15.880 alpha are on the placenta. So the same mechanisms 00:43:15.880 --> 00:43:18.599 that takes folate into the brain takes it across 00:43:18.599 --> 00:43:23.519 the placenta. And what we find is that a percentage, 00:43:23.760 --> 00:43:26.579 about half of the mothers of kids with the folate 00:43:26.579 --> 00:43:30.539 autoantibody have it themselves. So that means 00:43:30.539 --> 00:43:32.420 they may have had a double whammy. They may have 00:43:32.420 --> 00:43:35.820 had a problem getting folate into their body 00:43:35.820 --> 00:43:40.679 before birth and then after birth too. And so 00:43:40.679 --> 00:43:44.260 to prove this, Dr. Quartros developed an animal 00:43:44.260 --> 00:43:47.099 model where he takes, you know, pregnant rats 00:43:47.099 --> 00:43:50.480 and injects the folate autoantibody. And these 00:43:50.480 --> 00:43:55.340 are all different scales. of different tasks, 00:43:55.840 --> 00:43:58.800 passive avoidance, active avoidance, and such, 00:43:59.099 --> 00:44:01.320 and the performance on it. And you can see those 00:44:01.320 --> 00:44:05.679 that did not have the, that just got a sham did 00:44:05.679 --> 00:44:09.380 100%, whereas those that got the antibody either 00:44:09.380 --> 00:44:12.039 during gestation and pre -weaning, gestation 00:44:12.039 --> 00:44:14.340 or pre -weaning, that they failed on most of 00:44:14.340 --> 00:44:18.760 these tasks. And then what he did is he tried 00:44:18.760 --> 00:44:24.099 to rescue them. And so, We can see up here that 00:44:24.099 --> 00:44:32.000 these are a couple of different tasks. So average 00:44:32.000 --> 00:44:38.739 number of calls is essentially language. And 00:44:38.739 --> 00:44:43.559 so when the folate autoantibody was given to 00:44:43.559 --> 00:44:45.380 the mother here, you can see that the average 00:44:45.380 --> 00:44:50.239 number of calls decreased significantly. And 00:44:50.239 --> 00:44:54.880 if he gave either dexamethasone, a steroid, or 00:44:54.880 --> 00:44:57.920 phalaenic acid, leukovorin, you can see that 00:44:57.920 --> 00:45:00.860 all the pups, these are the pups that come out, 00:45:01.119 --> 00:45:05.659 they're all rescued in that behavior. And the 00:45:05.659 --> 00:45:08.579 same thing on a behavioral task too, as far as 00:45:08.579 --> 00:45:12.119 learning. So he showed you can actually rescue 00:45:12.119 --> 00:45:17.619 these pups during gestation while they're developing 00:45:17.619 --> 00:45:21.199 by giving the mother either high dose folic acid, 00:45:21.420 --> 00:45:25.760 leukoborin, or a steroid to decrease the inflammatory 00:45:25.760 --> 00:45:31.219 effect of the folate autoantibody. And then he's 00:45:31.219 --> 00:45:33.940 done other studies where he showed actually that 00:45:33.940 --> 00:45:37.139 the folate autoantibody causes inflammation. 00:45:37.579 --> 00:45:39.739 So this is a marker of inflammation, this brown 00:45:39.739 --> 00:45:42.659 stuff here. This is the placenta. And so you 00:45:42.659 --> 00:45:45.559 can see that there's inflammation when you have 00:45:45.559 --> 00:45:47.980 the folate autoantibody. And then he actually 00:45:47.980 --> 00:45:51.550 measured folate flux. and also showed that folate 00:45:51.550 --> 00:45:56.050 doesn't get into the fetus when you have these 00:45:56.050 --> 00:45:59.190 antibodies. One of the other interesting things 00:45:59.190 --> 00:46:01.409 that we found, which is a little complex, is 00:46:01.409 --> 00:46:04.769 that we saw that kids, we did a study and we 00:46:04.769 --> 00:46:08.190 found that the folate autoantibiotic was correlated 00:46:08.190 --> 00:46:12.329 with thyroid function. But the thyroid doesn't 00:46:12.329 --> 00:46:16.449 have the folate receptor alpha on it. And we 00:46:16.449 --> 00:46:19.690 said, huh, how can this be? And what we did is 00:46:19.690 --> 00:46:22.750 we actually took fetal tissue and we found that 00:46:22.750 --> 00:46:26.309 these brown spots are the folate receptor alpha. 00:46:27.030 --> 00:46:30.530 Then we found that up until 17 weeks gestation, 00:46:30.829 --> 00:46:37.650 the human thyroid actually does have the folate 00:46:37.650 --> 00:46:39.849 receptor alpha. So if your mother has the antibody, 00:46:40.469 --> 00:46:43.849 it's actually going to cause abnormalities in 00:46:43.849 --> 00:46:49.019 development of the thyroid. So yeah, so that's 00:46:49.019 --> 00:46:51.960 a little story of how I got into it in our journey 00:46:51.960 --> 00:46:54.360 so far and trying to figure out this mystery 00:46:54.360 --> 00:46:58.860 and figure out how to really help kids. That 00:46:58.860 --> 00:47:02.900 picture shown of the white matter of those brain 00:47:02.900 --> 00:47:06.480 scans was very wild. Yeah, that's very impressive. 00:47:07.000 --> 00:47:12.849 Yeah, that was a really good finding. With that 00:47:12.849 --> 00:47:15.289 language in the communication, do you think that's 00:47:15.289 --> 00:47:18.110 what it's doing, is increasing the white matter 00:47:18.110 --> 00:47:22.030 tracks from like Bronecki to Broca? Well, I think, 00:47:22.369 --> 00:47:27.489 yeah, I don't, it's, so yes, so there's a study, 00:47:27.570 --> 00:47:30.070 there's a nice study I didn't show, where they 00:47:30.070 --> 00:47:34.659 actually looked at changes in the brain. in the 00:47:34.659 --> 00:47:38.360 white matter with very sophisticated MRI techniques. 00:47:38.780 --> 00:47:40.980 And that's what they showed is that the improvement 00:47:40.980 --> 00:47:43.500 actually paralleled more development of the white 00:47:43.500 --> 00:47:46.199 matter. And so one of the things that we have 00:47:46.199 --> 00:47:49.300 to understand that's common about language and 00:47:49.300 --> 00:47:52.480 socialization is that they use parts of the brain 00:47:52.480 --> 00:47:54.980 that are really far away from each other. They 00:47:54.980 --> 00:47:56.559 use the back of the brain and the front of the 00:47:56.559 --> 00:48:00.119 brain. And so when the neurons aren't working 00:48:00.119 --> 00:48:02.920 well, it's very hard for them to synchronize 00:48:02.920 --> 00:48:05.679 those long distances. And if the white matter 00:48:05.679 --> 00:48:10.099 isn't in good shape. So those are probably why 00:48:10.099 --> 00:48:12.980 we see these symptoms in kids with autism. Because 00:48:12.980 --> 00:48:17.099 those particular higher level functioning are 00:48:17.099 --> 00:48:20.360 things that really need these. connections from, 00:48:20.360 --> 00:48:23.400 from, you know, places in the brain that are 00:48:23.400 --> 00:48:25.719 far away from each other. And it may be why we 00:48:25.719 --> 00:48:27.880 see some of them have certain splintered skills, 00:48:27.880 --> 00:48:30.460 right? Because like mathematics isn't really 00:48:30.460 --> 00:48:33.340 just one part of your brain, right? And so that 00:48:33.340 --> 00:48:36.000 can overdevelop, whereas the rest of the brain 00:48:36.000 --> 00:48:40.260 isn't developed. Yeah. Oh, my gosh, that those 00:48:40.260 --> 00:48:43.760 distal connections with that white matter track. 00:48:44.000 --> 00:48:46.960 Like maybe the arcuate fasciculus with the language 00:48:46.960 --> 00:48:51.539 track, I think, maybe is rescued. Yes, I would 00:48:51.539 --> 00:48:55.860 think so, yeah. Wow, that's impressive. Do you 00:48:55.860 --> 00:49:00.079 find that the leukovirin helps a certain type 00:49:00.079 --> 00:49:03.920 of the autistic phenotype, like the more severe 00:49:03.920 --> 00:49:06.920 versus the so -called higher functioning? Or 00:49:06.920 --> 00:49:09.940 is it pretty... straight forward across the the 00:49:09.940 --> 00:49:12.840 levels we use? Yeah, no, it's a great question. 00:49:14.460 --> 00:49:19.699 One thing we do find is that, well, one of our 00:49:19.699 --> 00:49:22.519 first studies suggested that the most severe 00:49:22.519 --> 00:49:24.860 children are the ones that didn't have language 00:49:24.860 --> 00:49:30.000 at all, you know, didn't benefit as much. But, 00:49:30.320 --> 00:49:32.900 you know, that's not what I see in some clinical 00:49:32.900 --> 00:49:35.280 practice. I see kids that are not talking, start 00:49:35.280 --> 00:49:41.989 talking, you know. And so it may be an artifact 00:49:41.989 --> 00:49:44.010 of the instruments we're using, because we can 00:49:44.010 --> 00:49:49.429 only measure things so far down. So that's the 00:49:49.429 --> 00:49:51.429 kind of where the clinical trials don't always 00:49:51.429 --> 00:49:54.349 tell you exactly what's going on. You're in a 00:49:54.349 --> 00:49:57.309 very controlled setting, an artificial setting, 00:49:57.630 --> 00:50:01.730 than the clinical practice. But the one thing 00:50:01.730 --> 00:50:04.960 that is really interesting is that We had many 00:50:04.960 --> 00:50:07.500 kids some that you know a lot of people are impressed 00:50:07.500 --> 00:50:10.639 going from not talking to talking of course But 00:50:10.639 --> 00:50:13.539 we found that even kids that were talking and 00:50:13.539 --> 00:50:17.019 could have conversations Luke of Orin would improve 00:50:17.019 --> 00:50:20.380 their ability to have their higher level, you 00:50:20.380 --> 00:50:25.139 know language abilities So the tests that we 00:50:25.139 --> 00:50:27.820 use get harder and harder and harder and we can 00:50:27.820 --> 00:50:31.239 measure some really sophisticated language abilities 00:50:31.239 --> 00:50:34.039 and it seems like they get better and better 00:50:34.039 --> 00:50:36.619 understanding and being able to produce things 00:50:36.619 --> 00:50:40.619 that are more nuanced as they're treated, even 00:50:40.619 --> 00:50:46.659 if they're talking to begin with. Okay, that's 00:50:46.659 --> 00:50:51.900 impressive. Brad? You answered my questions about 00:50:51.900 --> 00:50:55.440 the utero and the embryo genesis too and the 00:50:55.440 --> 00:51:00.199 neural tube. I found that the B9 and folate is 00:51:00.199 --> 00:51:03.460 huge for like the neural tube to the crest and 00:51:03.460 --> 00:51:08.420 neuralation and so forth. But yeah, you hit on 00:51:08.420 --> 00:51:11.099 those time frames and I think... So yeah, so 00:51:11.099 --> 00:51:12.619 that's, you know, that's what, you know, we're 00:51:12.619 --> 00:51:15.079 trying to move forward as I think I told you 00:51:15.079 --> 00:51:16.639 I'm going to have a book coming out called The 00:51:16.639 --> 00:51:21.480 Folate Fix. which has about a dozen stories from 00:51:21.480 --> 00:51:25.340 parents. So it's not just me, it's a lot of stories 00:51:25.340 --> 00:51:27.800 from parents. So you can see what people's journeys 00:51:27.800 --> 00:51:32.099 are like and their struggles. And I hope that 00:51:32.099 --> 00:51:35.239 will help parents understand things, understand 00:51:35.239 --> 00:51:38.400 the struggles that parents go through to get 00:51:38.400 --> 00:51:41.679 their kid recovered. So that's one way that we're 00:51:41.679 --> 00:51:45.400 trying to get the word out. A lot of physicians 00:51:45.400 --> 00:51:48.289 are very interested in how to use it. So part 00:51:48.289 --> 00:51:51.650 of that book has kind of a guideline for doing 00:51:51.650 --> 00:51:56.750 that. We're hoping to get some learning sessions, 00:51:56.750 --> 00:52:01.030 videos up to be more of a training session, more 00:52:01.030 --> 00:52:04.230 of a CME course for physicians. And then the 00:52:04.230 --> 00:52:06.849 other thing going to what you're talking about 00:52:06.849 --> 00:52:09.630 with gestation right now, what we're doing is 00:52:09.630 --> 00:52:12.550 we have a grant from the Arizona State to look 00:52:12.550 --> 00:52:16.679 at something called transgenerational. aspects 00:52:16.679 --> 00:52:19.539 of the folate order antibody, because what we 00:52:19.539 --> 00:52:26.760 find is that these run in families. And so this 00:52:26.760 --> 00:52:29.440 may be, you know, one of the mysteries with autism 00:52:29.440 --> 00:52:34.780 is that there's a very big heritability to it. 00:52:34.940 --> 00:52:38.239 And so everybody equates that to genetics, right? 00:52:39.239 --> 00:52:41.320 But genetics is only one type of heritability. 00:52:41.900 --> 00:52:44.940 And so we're finding these other disorders that 00:52:44.940 --> 00:52:48.119 are non genetic, at least not purely genetic, 00:52:48.420 --> 00:52:50.840 heritable conditions. And of course, the great 00:52:50.840 --> 00:52:53.619 thing is that we can, if we find them, then we 00:52:53.619 --> 00:52:55.739 can treat them and we can treat them from the 00:52:55.739 --> 00:52:59.360 beginning, you know, before the woman's pregnant, 00:52:59.539 --> 00:53:01.539 really, that's, that's where you want to start. 00:53:01.760 --> 00:53:04.440 And the man, we find that also that the folate 00:53:04.440 --> 00:53:06.880 auto antibody in dad seems to have an effect 00:53:06.880 --> 00:53:12.840 too. So, so yeah, so both women and men, you 00:53:12.840 --> 00:53:14.920 know, we want to get them prepared. you know, 00:53:14.920 --> 00:53:16.780 to become pregnant because, you know, that's 00:53:16.780 --> 00:53:19.500 what I try and explain to moms. They have another 00:53:19.500 --> 00:53:21.440 child that as soon as you get pregnant, you're 00:53:21.440 --> 00:53:24.099 putting a lot of pressure on your body and taking 00:53:24.099 --> 00:53:26.559 out all the resources. So you got to build up 00:53:26.559 --> 00:53:29.860 those resources to begin with. Yeah, the environment 00:53:29.860 --> 00:53:32.760 of the pregnant mother has vastly changed so 00:53:32.760 --> 00:53:37.500 much. Um, and I don't want to jump to conclusions 00:53:37.500 --> 00:53:39.699 here, but maybe there's a role with like spinal 00:53:39.699 --> 00:53:42.420 bifida. Yeah. Oh yeah. Yeah. Most definitely 00:53:42.420 --> 00:53:46.230 is. Yeah. Yeah. Yeah. Okay, yeah. Yeah, so that's, 00:53:46.269 --> 00:53:48.690 yeah, so that's where Dr. Quattro started out, 00:53:48.809 --> 00:53:51.230 you know, so it's kind of funny how things have 00:53:51.230 --> 00:53:55.829 kind of come full circle. Yes, yeah, that's so 00:53:55.829 --> 00:54:00.849 incredible. Because, wow, how does somebody go 00:54:00.849 --> 00:54:05.250 about maybe their autistic, or, as you described, 00:54:05.329 --> 00:54:07.610 they're preparing for pregnancy, or they do have 00:54:07.610 --> 00:54:09.730 an autistic child, maybe it's a parent, how do 00:54:09.730 --> 00:54:19.539 they go about trying to So what I usually suggest 00:54:19.539 --> 00:54:22.239 like the basic things is so we have something 00:54:22.239 --> 00:54:27.320 called the Neurologic Health Foundation and that's 00:54:27.320 --> 00:54:30.159 and some great people on there like Jim Adams 00:54:30.159 --> 00:54:32.579 and such and we've put together something called 00:54:32.579 --> 00:54:36.260 the Healthy Child Guide. So you can just Google 00:54:36.260 --> 00:54:38.920 that the Neurologic Health Foundation Healthy 00:54:38.920 --> 00:54:41.400 Child Guide and it's a guide we put together 00:54:41.400 --> 00:54:44.210 based on science. of what things you should do 00:54:44.210 --> 00:54:46.929 to prepare for and to do during your pregnancy 00:54:46.929 --> 00:54:50.469 to keep yourself healthy. The other thing that's 00:54:50.469 --> 00:54:54.449 really important is to get a multivitamin that's 00:54:54.449 --> 00:54:58.349 very complete and also has reduced folates in 00:54:58.349 --> 00:55:04.909 it. So one of the problems with many of the prenatal 00:55:04.909 --> 00:55:10.710 vitamins is that since folic acid is the only 00:55:10.710 --> 00:55:14.340 thing scientifically that has been shown to reduce 00:55:14.340 --> 00:55:18.239 neurotube defects. Many of the manufacturers 00:55:18.239 --> 00:55:24.219 won't change to a reduced folate, right? Because 00:55:24.219 --> 00:55:27.920 legalistically, you know, it's the only thing, 00:55:28.099 --> 00:55:30.260 folic acid is the only thing that's been proven. 00:55:30.400 --> 00:55:32.519 We don't have the data on these reduced folates. 00:55:32.960 --> 00:55:37.480 But we know that these reduced folates are equivalent 00:55:37.480 --> 00:55:40.750 or better, and probably better. Because the other 00:55:40.750 --> 00:55:43.510 thing we're finding about folic acid is, you 00:55:43.510 --> 00:55:46.010 know, as I was saying, we only have a limited 00:55:46.010 --> 00:55:49.429 ability to actually reduce it and make it into 00:55:49.429 --> 00:55:52.730 its active form. And so this is kind of one of 00:55:52.730 --> 00:55:55.530 the mysteries, right, is that there's a study 00:55:55.530 --> 00:55:59.010 that shows that folic acid supplementation prevents 00:55:59.010 --> 00:56:02.289 autism, folic acid supplementation during pregnancy, 00:56:02.789 --> 00:56:06.130 you know, decreases the risk of autism. But then 00:56:06.130 --> 00:56:09.800 when they measure folate levels, mother's broad, 00:56:10.820 --> 00:56:13.840 higher folate levels are correlated with greater 00:56:13.840 --> 00:56:18.019 risk of autism. So that doesn't quite make sense 00:56:18.019 --> 00:56:21.460 on the surface and then you find out that those 00:56:21.460 --> 00:56:25.300 greater levels of folate was unmetabolized folic 00:56:25.300 --> 00:56:30.980 acid. So that's the problem is that scientifically 00:56:30.980 --> 00:56:34.940 too we're finding that folic acid at high levels 00:56:34.940 --> 00:56:39.719 will actually inhibit the folate cycle. So when 00:56:39.719 --> 00:56:42.599 it gets too high, it can have detrimental effects. 00:56:43.079 --> 00:56:45.519 So that's why we can't just give more folic acid. 00:56:45.739 --> 00:56:47.800 We have to give what we call reduced folate. 00:56:48.260 --> 00:56:52.219 So methotetrahydrofolate, tetrahydrofolate, leucovorin, 00:56:52.340 --> 00:56:55.760 and such. So that those go right into the folate 00:56:55.760 --> 00:56:59.019 cycle. So we know from experiments that those 00:56:59.019 --> 00:57:01.199 type of folates don't inhibit the folate cycle. 00:57:01.239 --> 00:57:07.800 So you can give higher doses. Wow, okay. So yeah, 00:57:07.800 --> 00:57:10.420 so definitely get a prenatal that has reduced 00:57:10.420 --> 00:57:14.099 folates in it. And there's several good ones 00:57:14.099 --> 00:57:16.800 that have been made by high quality supplement 00:57:16.800 --> 00:57:19.840 companies. Look for the Healthy Child Guide, 00:57:19.840 --> 00:57:24.280 you know, and make sure that you plan things 00:57:24.280 --> 00:57:29.920 well. Yeah, there's so much that's come out about 00:57:29.920 --> 00:57:33.539 that. When could we expect you to book the folate 00:57:33.539 --> 00:57:39.869 fix? Probably about a month. Oh, wow. Okay. So 00:57:39.869 --> 00:57:43.409 yeah, you can come to my website, autism discovery 00:57:43.409 --> 00:57:48.489 .org and sign up for a notice when we get it. 00:57:48.869 --> 00:57:51.409 So yeah, you know, fight about things. I spread 00:57:51.409 --> 00:57:57.090 that on social media too. And these links and 00:57:57.090 --> 00:58:00.829 these organizations that you talked about. Sure. 00:58:00.929 --> 00:58:03.349 Yeah, we're on Facebook and TikTok. So if you 00:58:03.349 --> 00:58:05.610 want to follow us. You know, follow, like, and 00:58:05.610 --> 00:58:09.250 share and all that type of stuff. For my discussions 00:58:09.250 --> 00:58:13.750 with you and Nicole, I've learned so much about 00:58:13.750 --> 00:58:17.809 how these different things with the folic, versus 00:58:17.809 --> 00:58:21.150 the folate, versus the fol... I mean, there's 00:58:21.150 --> 00:58:25.730 just so much that's, people, I don't know, it's 00:58:25.730 --> 00:58:29.489 hard to discover. Yeah, it's kind of hard to 00:58:29.489 --> 00:58:34.909 imagine that vitamins are so complicated. Yeah, 00:58:34.909 --> 00:58:37.829 especially the B9. It seems like the B9 is really 00:58:37.829 --> 00:58:41.269 complicated. Well, it's important. I think, you 00:58:41.269 --> 00:58:43.530 know, there's certain, you know, vitamins like 00:58:43.530 --> 00:58:47.530 B9, B12, and such that that are central to so 00:58:47.530 --> 00:58:51.389 many different mechanisms that they're so important. 00:58:51.869 --> 00:58:55.329 Mm -hmm. Yeah. And when you're deficient, it's 00:58:55.329 --> 00:58:58.570 so much goes wrong, you know? Yeah, yeah. Downstream, 00:58:59.250 --> 00:59:01.750 it could show up. It manifests as a lot of different 00:59:01.750 --> 00:59:06.079 things, I think. Is there anything else that 00:59:06.079 --> 00:59:09.780 you would like to share or mention before you 00:59:09.780 --> 00:59:12.679 wrap up? Yeah, you know, I mean, I think the 00:59:12.679 --> 00:59:15.380 important thing is, you know, this is a great 00:59:15.380 --> 00:59:18.119 treatment. You know, I hope people, you know, 00:59:18.400 --> 00:59:20.340 find out, tell their doctors about it. You know, 00:59:20.460 --> 00:59:22.400 that's where doctors a lot of times find out 00:59:22.400 --> 00:59:24.699 about it, about, you know, people bringing them 00:59:24.699 --> 00:59:27.679 the research, bring the research papers, you 00:59:27.679 --> 00:59:30.659 know, not just a news article because they, you 00:59:30.659 --> 00:59:35.000 know. And then, you know, I think always the 00:59:35.000 --> 00:59:38.679 important thing, you know, of any of the journeys, 00:59:38.679 --> 00:59:41.500 you know, is for parents to know that it's not 00:59:41.500 --> 00:59:44.800 a sprint, it's a marathon, and it takes a lot 00:59:44.800 --> 00:59:51.099 of work, but you can get there. Yeah. Nicole 00:59:51.099 --> 00:59:55.420 mentioned that about the duration of taking these 00:59:55.420 --> 00:59:58.260 things, and people will give up on them fast. 00:59:58.579 --> 01:00:02.440 Yeah. So it's important to have the guidance 01:00:02.440 --> 01:00:04.880 of somebody. I know a lot of parents want to 01:00:04.880 --> 01:00:07.219 do things fast. They say, oh, I can get phalamic 01:00:07.219 --> 01:00:10.000 acid over the counter. I'm just going to try 01:00:10.000 --> 01:00:12.260 it. Oh, I don't want to do the full eight auto 01:00:12.260 --> 01:00:14.800 antibody test. But it's kind of important to 01:00:14.800 --> 01:00:17.320 do all of these, because it's not that simple. 01:00:17.320 --> 01:00:19.840 And you can fail in many different ways. And 01:00:19.840 --> 01:00:23.900 you want some type of guidance to know what is 01:00:23.900 --> 01:00:26.820 the next step. Many times, we find that Leucovore 01:00:26.820 --> 01:00:30.719 doesn't work alone. that it needs either cortotine, 01:00:31.000 --> 01:00:34.539 PQQ, vitamin D, you know, other types of things. 01:00:34.579 --> 01:00:36.699 If there's mitochondrial issues, you have to 01:00:36.699 --> 01:00:40.820 address those. So it's not so, you know, it's 01:00:40.820 --> 01:00:45.059 not so easy. And this isn't the autism pill, 01:00:45.400 --> 01:00:48.019 you know, that a lot of patients, you know, I 01:00:48.019 --> 01:00:49.360 have patients that haven't come back because 01:00:49.360 --> 01:00:51.099 they told me, well, you didn't give me the autism 01:00:51.099 --> 01:00:57.119 pill. Well, there's no autism pill. It's a work, 01:00:57.260 --> 01:00:59.940 it's complex, and it's great to have somebody 01:00:59.940 --> 01:01:02.980 to guide you through it. Yeah. Yeah. Yeah. Thank 01:01:02.980 --> 01:01:07.699 you for sharing all this information. We'll definitely 01:01:07.699 --> 01:01:09.980 be on the lookout for your research, because 01:01:09.980 --> 01:01:13.460 I learned about Luca Horan from your first episode, 01:01:13.860 --> 01:01:15.920 whenever I asked you what recently are you most 01:01:15.920 --> 01:01:18.219 interested in, this was the first thing that 01:01:18.219 --> 01:01:21.760 you mentioned. And then, obviously, the last 01:01:21.760 --> 01:01:25.159 couple of weeks, it's hit. the news. So this 01:01:25.159 --> 01:01:27.719 is really fantastic. Yeah, we're very lucky that 01:01:27.719 --> 01:01:30.960 yeah, CBS, you know, picked it up and we've gotten 01:01:30.960 --> 01:01:33.800 a lot of good press from that. Yeah. Yeah, I'll 01:01:33.800 --> 01:01:36.079 do my best of sharing this information to you 01:01:36.079 --> 01:01:38.420 because I think it's worthy with that low risk 01:01:38.420 --> 01:01:42.460 high reward type of thing. Yeah. Well, Dr. Fried, 01:01:42.480 --> 01:01:46.099 thank you for joining again and looking forward 01:01:46.099 --> 01:01:49.840 to maybe another future interaction with you 01:01:49.840 --> 01:01:55.199 all the time. Yeah, always happy. to beyond spread 01:01:55.199 --> 01:01:58.199 the good word. Yeah, yeah, yeah. We appreciate 01:01:58.199 --> 01:02:03.340 that. Have a good day and thank you so much. 01:02:03.960 --> 01:02:06.739 All right. Take care. Thanks. Bye.